Cytotoxic T lymphocytes (CTLs) have been shown to recognize epitope peptides derived from tumor-associated antigens (TAAs) found on major the histocompatibility complex (MHC) class I molecule, and then kill the tumor cells. Since the discovery of the melanoma antigen (MAGE) family, many other TAAs have been discovered through immunological approaches (NPL 1, Boon T, Int J Cancer 1993 May 8, 54(2): 177-80; NPL 2, Boon T & van der Bruggen P, J Exp Med 1996 Mar. 1, 183(3): 725-9). Some of these TAAs are currently undergoing clinical development as immunotherapeutic targets.
Favorable TAAs are indispensable for the proliferation and survival of cancer cells. The use of such TAAs as targets for immunotherapy may minimize the well-described risk of immune escape of cancer cells attributable to deletion, mutation, or down-regulation of TAAs as a consequence of therapeutically driven immune selection. Accordingly, the identification of new TAAs capable of inducing potent and specific anti-tumor immune responses, warrants further development and thus the clinical application of peptide vaccination strategies for various types of cancer is ongoing (NPL 3, Harris C C, J Natl Cancer Inst 1996 Oct. 16, 88(20): 1442-55; NPL 4, Butterfield L H et al., Cancer Res 1999 Jul. 1, 59(13): 3134-42; NPL 5, Vissers J L et al., Cancer Res 1999 Nov. 1, 59(21): 5554-9; NPL 6, van der Burg S H et al., J Immunol 1996 May 1, 156(9): 3308-14; NPL 7, Tanaka F et al., Cancer Res 1997 Oct. 15, 57(20): 4465-8; NPL 8, Fujie T et al., Int J Cancer 1999 Jan. 18, 80(2): 169-72; NPL 9, Kikuchi M et al., Int J Cancer 1999 May 5, 81(3): 459-66; NPL 10, Oiso M et al., Int J Cancer 1999 May 5, 81(3): 387-94). To date, several clinical trials using these tumor-associated antigen derived peptides have been reported. Unfortunately, many of the current cancer vaccine trial have shown only a low objective response rate (NPL 11, Belli F et al., J Clin Oncol 2002 Oct. 15, 20(20): 4169-80; NPL 12, Coulie P G et al., Immunol Rev 2002 October, 188: 33-42; NPL 13, Rosenberg S A et al., Nat Med 2004 September, 10(9): 909-15). Accordingly, there remains a need in the art for new TAAs as immunotherapeutic targets.
MPHOSPH1 (M-phase phosphoprotein 1; GenBank Accession No. NM_016195 and NP_057279, SEQ ID NO: 125 and 126), was identified as one of the proteins specifically phosphorylated at the G2/M transition and characterized as a plus-end-directed kinesin related protein (NPL 14, Abaza A et al., J Biol Chem 2003, 278: 27844-52.). More particularly, MPHOSPH1 has been reported to be a plus-end-directed molecular motor that plays a crucial role in cytokinesis, and accumulates in the midzone of the spindle during anaphase to telophase in HeLa cells (NPL 14, Abaza A et al., J Biol Chem 2003, 278: 27844-52; NPL 15, Kamimoto T et al., J Biol Chem 2001, 276: 37520-8). In the course of gene expression profile analyses using a genome-wide cDNA microarray containing 23,040 genes, MPHOSPH1 was identified as a novel molecule up-regulated in bladder cancer (NPL 16, Kanehira M et al., Cancer Res. 2007 Apr. 1; 67(7):3276-85; PTL 1, WO2006/085684). Furthermore, through northern blot analysis, expression of the MPHOSPH1 gene products were found to be limited to the testis and absent from the normal vital organs.
Some peptide fragments derived from MPHOSPH1 having cytotoxic T lymphocyte (CTL) inducibility were previously identified (PTL 2, WO2008/047473). These peptide fragments demonstrated the ability to induce CTLs against cells stimulated with the cognate peptide fragments. However, previous studies failed to confirm whether the peptide fragments had the ability to induce CTLs targeting tumor cells expressing the MPHOSPH1 gene and HLA-A2 antigen.